The cholinergic system and Parkinson disease.
The cholinergic system and Parkinson disease.
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DOI：
10.1016/j.bbr.2009.12.048
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发表时间：
2011-08-10
影响因子：
2.7
通讯作者：
Albin, Roger L.
中科院分区：
文献类型：
--
作者：
Bohnen, Nicolaas I.;Albin, Roger L.
关键词：
虽然帕金森病（PD）传统上被认为是一种运动综合征继发于黑质纹状体多巴胺能神经，最近的研究强调非运动功能。非运动共病（如认知障碍）可能是多系统变性和神经递质缺乏（超出多巴胺能黑质神经元损失）复杂相互作用的结果。帕金森氏痴呆的病理学标志是黑质外路易体的存在，其可伴有其他病理，如老年斑。路易首先在Meynert基底核（nbM）的神经元中发现了上皮路易体，这是大脑皮层胆碱能神经支配的来源。虽然胆碱能神经支配被认为是阿尔茨海默病（AD）的病理标志，在体内的神经影像学研究显示，在帕金森氏症痴呆症的大脑胆碱能标记物的损失类似或更严重的比原型AD。影像学研究与尸检证据一致，表明基底前脑胆碱能系统变性出现在PD和PD的早期，与痴呆的出现一致。早期胆碱能去神经在PD无痴呆似乎是异质性的，并可能作出具体的贡献PD的临床表型。除了众所周知的认知和行为缺陷，中央，特别是边缘，胆碱能去神经支配可能与渐进性缺陷的气味识别在PD。最近的证据也表明，皮质下胆碱能神经支配，可能是由于脑干脚桥核神经元的变性，可能与多巴胺无反应步态和平衡障碍，包括福尔斯，在PD的存在。
Although Parkinson disease (PD) is viewed traditionally as a motor syndrome secondary to nigrostriatal dopaminergic denervation, recent studies emphasize non-motor features. Non-motor comorbidities, such as cognitive impairment, are likely the result of an intricate interplay of multi-system degenerations and neurotransmitter deficiencies extending beyond the loss of dopaminergic nigral neurons. The pathological hallmark of parkinsonian dementia is the presence of extra-nigral Lewy bodies that can be accompanied by other pathologies, such as senile plaques. Lewy first identified the eponymous Lewy body in neurons of the nucleus basalis of Meynert (nbM), the source of cholinergic innervation of the cerebral cortex. Although cholinergic denervation is recognized as a pathological hallmark of Alzheimer disease (AD), in vivo neuroimaging studies reveal loss of cerebral cholinergic markers in parkinsonian dementia similar to or more severe than in prototypical AD. Imaging studies agree with post-mortem evidence suggesting that basal forebrain cholinergic system degeneration appears early in PD and worsens coincident with the appearance of dementia. Early cholinergic denervation in PD without dementia appears to be heterogeneous and may make specific contributions to the PD clinical phenotype. Apart from well-known cognitive and behavioral deficits, central, in particular limbic, cholinergic denervation may be associated with progressive deficits of odor identification in PD. Recent evidence indicates also that subcortical cholinergic denervation, probably due to degeneration of brainstem pedunculopontine nucleus neurons, may relate to the presence of dopamine non-responsive gait and balance impairments, including falls, in PD.
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